A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Sandostatin Pharmacology, Pharmacokinetics, Studies, Metabolism - Octreotide (Injection)
Sandostatin Pharmacology, Pharmacokinetics, Studies, Metabolism - Octreotide (Injection)
CLINICAL PHARMACOLOGY
Sandostatin® (octreotide acetate) exerts pharmacologic
actions similar to the natural hormone, somatostatin. It is an even more
potent inhibitor of growth hormone, glucagon, and insulin than somatostatin.
Like somatostatin, it also suppresses LH response to GnRH, decreases splanchnic
blood flow, and inhibits release of serotonin, gastrin, vasoactive intestinal
peptide, secretin, motilin, and pancreatic polypeptide.
By virtue of these pharmacological actions, Sandostatin®
(octreotide acetate) has been used to treat the symptoms associated with
metastatic carcinoid tumors (flushing and diarrhea), and Vasoactive Intestinal
Peptide (VIP) secreting adenomas (watery diarrhea).
Sandostatin® (octreotide acetate) substantially reduces
growth hormone and/or IGF-I (somatomedin C) levels in patients with acromegaly.
Single doses of Sandostatin® (octreotide acetate) have
been shown to inhibit gallbladder contractility and to decrease bile secretion
in normal volunteers. In controlled clinical trials the incidence of gallstone
or biliary sludge formation was markedly increased (See WARNINGS).
Sandostatin® (octreotide acetate) suppresses secretion
of thyroid stimulating hormone (TSH).
Pharmacokinetics
After subcutaneous injection, octreotide is absorbed rapidly and completely
from the injection site. Peak concentrations of 5.2 ng/mL( 100 mcg dose)
were reached 0.4 hours after dosing. Using a specific radio immunoassay,
intravenous and subcutaneous doses were found to be bioequivalent. Peak
concentrations and area under the curve values were dose proportional
both after subcutaneous or intravenous single doses up to 400 mcg and
with multiple doses of 200 mcg t.i.d. (600 mcg/day). Clearance was reduced
by about 66% suggesting non-linear kinetics of the drug at daily doses
of 600 mcg/day as compared to 150 mcg/day. The relative decrease in clearance
with doses above 600 mcg/day is not defined.
In healthy volunteers the distribution of octreotide from plasma was
rapid (ta
1/2= 0.2 h), the volume of distribution (Vdss) was estimated
to be 13.6 L, and the total body clearance was 10 L/hr.
In blood, the distribution into the erythrocytes was found to be negligible
and about 65% was bound in the plasma in a concentration-independent manner.
Binding was mainly to lipoprotein and, to a lesser extent, to albumin.
The elimination of octreotide from plasma had an apparent half-life of
1.7 hours compared with 1-3 minutes with the natural hormone. The duration
of action of Sandostatin® (octreotide acetate) invariable
but extends up to 12 hours depending upon the type of tumor. About 32%
of the dose is excreted unchanged into the urine. In an elderly population,
dose adjustments may be necessary due to a significant increase in the
half-life (46%) and a significant decrease in the clearance (26%) of the
drug.
In patients with acromegaly, the pharmacokinetics differ somewhat from
those in healthy volunteers. A mean peak concentration of 2.8 ng/mL (100
mcg dose) was reached in 0.7 hours after subcutaneous dosing. The volume
of distribution (Vdss) was estimated to be 21.6±8.5 L and the total body
clearance was increased to 18 L/h. The mean percent of the drug bound
was 41.2%. The disposition and elimination half-lives were similar to
normals.
In patients with severe renal failure requiring dialysis, clearance was
reduced to about half that found in normal subjects (from approximately
10 L/h to 4.5 L/h). The effect of hepatic diseases on the disposition
of octreotide is unknown.
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